Investigative Interests

Ongoing Research

Metabolic syndrome (MetS) affects one of every three Americans and dramatically increases their risk for cardiovascular disease. Individual phenotypic components of MetS such as skewed body fat distribution and insulin resistance are consequences of the dynamic interaction between nature (the genome) and nurture (the environment). Genomic CpG methylation status, an epigenetic regulator of gene expression, is one of the prominent mechanistic links between the genome and the environment. Studying the quantitative relationship of MetS traits and genomic methylation status is therefore likely to unravel genetic elements and pathways that have not been identified by previous genomic studies focusing on primary sequence variants.

The TOPS Obesity and Metabolic Research Center possess a unique study population that consists of multi-generational extended families of Northern European origin that have been phenotyped for 42 clinical and biological components of the MetS. These large pedigrees also contain children undergoing puberty, a crucial stage in the development of MetS in adults. I am interested in applying state-of-the-art high throughput genomic technologies to the investigation of pathogenesis of MetS using this unique population. We have recently proposed to study the relationship between regional and global DNA methylation and these 42 MetS phenotypes in these families. By combining genome-wide SNP genotype data as well as genome-wide gene expression data of the most informative pedigrees, we will be able to prioritize our candidate genes for the detailed CpG methylation study.

We hope to create a new map of MetS epigenetic markers by using our unique suite of expertise in human and animal systems. By using related human subjects and inbred mouse strains, we aim to assess heritability of CpG methylation as well as diet-, age- and sex- effects on this epigenetic feature. This will enable us to identify the epigenetic loci that can integrate environmental cues in triggering pathophysiological pathways leading to MetS, a cluster of high-risk factors for type 2 diabetes, CV disease and cancer.